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Published on: October 25, 2019
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A yeast chemogenomic screen identifies pathways that modulate adipic acid toxicity
Eugene Fletcher1, Kevin Mercurio1, Elizabeth A Walden1
1Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada.
Iscience
|April 23, 2021
Summary
Yeast fermentation of adipic acid, a nylon precursor, is hindered by its toxicity. Deleting the KGD1 gene enhances yeast tolerance, while disrupting ergosterol and protein trafficking increases sensitivity, revealing key cellular targets for improving production.
Area of Science:
- Biotechnology
- Chemical Engineering
- Molecular Biology
Background:
- Yeast fermentation offers a sustainable route to adipic acid, a key nylon precursor.
- Adipic acid and its precursors exhibit toxicity, limiting yeast fermentation efficiency.
- Understanding cellular mechanisms of adipic acid toxicity is crucial for optimizing production.
Purpose of the Study:
- To identify yeast genes and cellular pathways involved in adipic acid tolerance.
- To elucidate the molecular basis of adipic acid toxicity in *Saccharomyces cerevisiae*.
- To provide insights for engineering yeast strains with enhanced adipic acid production capabilities.
Main Methods:
- Conducted a chemogenomic screen in *Saccharomyces cerevisiae* to assess adipic acid tolerance.
- Utilized gene deletion libraries to identify genes conferring sensitivity or resistance.
- Investigated the impact of adipic acid on membrane integrity and endocytic pathways.
Main Results:
- Deletion of *KGD1*, a tricarboxylic acid cycle gene, significantly improved tolerance to adipic acid and catechol.
- Disruption of ergosterol biosynthesis and protein trafficking pathways led to hypersensitivity to adipic acid.
- Adipic acid was shown to disrupt the Membrane Compartment of Can1 (MCC) and impair endocytosis, evidenced by Can1 internalization.
Conclusions:
- The *KGD1* gene is a key determinant of adipic acid tolerance in yeast.
- Ergosterol biosynthesis and protein trafficking/vacuolar transport are critical for mitigating adipic acid toxicity.
- Targeting these cellular processes offers a strategy for enhancing renewable adipic acid production.
